Inhibitors of angiotensin-converting enzyme have been shown to have great potential as anti-hypertensive drugs. A number of clinically promising angiotensin-converting enzyme (ACE) inhibitors contain as a common structural component, the molecule L-4-phenyl-2-aminobutanoic acid. This molecule is an "unnatural" L-amino acid, with a structure analogous to the 20 natural L-amino acids.
Methods currently in use for the production of amino acids include extraction, chemical synthesis followed by resolution, fermentation and enzymatic synthesis (biocatalysis). Extraction procedures require extensive purification of the amino acid of interest from protein hydrolyzates. With chemical synthetic methods, normally a racemic mixture is formed, and the resolution to produce the optically active product is often costly and inefficient. Fermentation, while overcoming many of the disadvantages inherent in the previously mentioned methods, suffers from problems of slow rates of conversion, dilute solutions, costly purifications, and very high capital costs. Biocatalysis offers the potential for lower cost production in many cases primarily because of the significantly reduced capital requirements, lower purification costs due to the absence byproducts in the product stream, and higher rates of conversion of substrates to products because fewer enzymatic steps are involved.
Currently, L-4-phenyl-2-aminobutanoic acid is produced by classical chemical resolutions of the D,L-mixture. The unused D-isomer may be either racemized and recycled or discarded. It would be highly desirable to have a process that produces only the L-isomer directly in essentially quantitative yields in a single reaction step.